Burst Kinetics of Co-expressed Kir6.2/SUR1 Clones: Comparison of Recombinant with Native ATP-sensitive K+ Channel Behavior |
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Authors: | AE Alekseev ME Kennedy B Navarro A Terzic |
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Institution: | (1) Division of Cardiovascular Diseases, Guggenheim 7F, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA, US;(2) Department of Pharmacology, Guggenheim 7F, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA, US |
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Abstract: | Co-expression of clones encoding Kir6.2, a K+ inward rectifier, and SUR1, a sulfonylurea receptor, reconstitutes elementary features of ATP-sensitive K+ (KATP) channels. However, the precise kinetic properties of Kir6.2/SUR1 clones remain unknown. Herein, intraburst kinetics of Kir6.2/SUR1
channel activity, heterologously co-expressed in COS cells, displayed mean closed times from 0.7 ± 0.1 to 0.4 ± 0.03 msec,
and from 0.4 ± 0.1 to 2.0 ± 0.2 msec, and mean open times from 1.9 ± 0.4 to 4.5 ± 0.8 msec, and from 12.1 ± 2.4 to 5.0 ± 0.2
msec between −100 and −20 mV, and +20 to +80 mV, respectively. Burst duration for Kir6.2/SUR1 activity was 17.9 ± 1.8 msec
with 5.6 ± 1.5 closings per burst. Burst kinetics of the Kir6.2/SUR1 activity could be fitted by a four-state kinetic model defining transitions between
one open and three closed states with forward and backward rate constants of 1905 ± 77 and 322 ± 27 sec−1 for intraburst, 61.8 ± 6.6 and 23.9 ± 5.8 sec−1 for interburst, 12.4 ± 6.0 and 13.6 ± 2.9 sec−1 for intercluster events, respectively. Intraburst kinetic properties of Kir6.2/SUR1 clones were essentially indistinguishable
from pancreatic or cardiac KATP channel phenotypes, indicating that intraburst kinetics per se were insufficient to classify recombinant Kir6.2/SUR1 amongst native KATP channels. Yet, burst kinetic behavior of Kir6.2/SUR1 although similar to pancreatic, was different from that of cardiac KATP channels. Thus, expression of Kir6.2/SUR1 proteins away from the pancreatic micro-environment, confers the burst kinetic
identity of pancreatic, but not cardiac KATP channels. This study reports the kinetic properties of Kir6.2/SUR1 clones which could serve in the further characterization
of novel KATP channel clones.
Received: 12 March 1997/Revised: 5 May 1997 |
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Keywords: | : KATP channels — Kinetic model — Inward rectifier K+ channel — ABC binding cassette — Pancreas — Cardiac |
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